Effects of selected plasma lidocaine concentrations on the action potentials of isolated canine Purkinje fibers were studied with microelectrode techniques and a method for perfusing PF with the arterial blood of a normokalemic dog. Lidocaine was administered to the donor as an intravenous injection of 0.5 to 2.0 mg. per kilogram or as an intravenous infusion of 4 to 50 mug per kilogram per minute and plasma concentrations were determined by gas chromatography. At plasma lidocaine concentrations from 0.2 to 9.9 mug per milliliter no significant changes in donor arterial pressure, heart rate, or electrocardiographic P-R and QRS intervals occurred, and Purkinje fiber resting membrane potential was unchanged. Donor Q-T intervals were unchanged at lower lidocaine concentrations (up to 4.0 mug per milliliter) and decreased at higher levels (4.1 to 9.9 mug per milliliter). Purkinje fiber AP changes commenced in 2 to 3 minutes of lidocaine injection. At lower lidocaine levels AP amplitude, maximum slope of phase 0 depolarization (Vmax) AP duration, and effective refractory period decreased, membrane responsiveness was depressed, and automaticity of spontaneously firing Purkinje fibers decreased. These changes were accentuated at higher lidocaine concentrations. Conduction usually was unchanged or slowed at lower plasma lidocaine levels and slowed at higher concentrations. When ouabain-intoxicated preparations were studied, lidocaine exerted a depressant effect on the AP. These studies indicate that the mechanisms whereby therapeutic lidocaine concentrations may modify arrhythmias are not unlike those of other local anesthetics and include depression of Vmax, membrane responsiveness, and conduction.